Vitamin D Deficiency:

The Crucial Hormonal Imbalance

Gary E. Foresman, MD

Middle Path Medicine 180 W Le Point St. Unit A

Arroyo Grande, CA 93420

805-481-3442

www.middlepathmedicine.com

info@middlepathmedicine.com

Physiology of Vitamin D

• Vitamin D (cholecalciferol) is formed in the skin

from exposure to sunlight.

• Then it is converted in the liver to 25-

hydroxyvitamin D (calcidiol, 25(OH)D) by the

enzyme vitamin D-25-hydroxylase.

• 25(OH)D then is transformed in the kidney to

1,25-dihydroxyvitamin D (calcitriol) by 25-

hydroxyvitamin D3-1alpha-hydroxylase (1-

OHase).

Vitamin D Vocabulary

Vitamin D3 = Cholecalciferol

Vitamin D2 = Ergocalciferol

25 Hydroxy Vitamin D3 = 25(OH) D3 =

25(OH)D = 25 Hydroxy Cholecalciferol =

Calcidiol = Vitamin D blood test = Vitamin D

serum level

1, 25 Dihydroxy Vitamin D3 = 1,25(OH)2D

1, 25 Dihydroxy Cholecalciferol = Calcitriol

Vitamin D Math

• 1 microgram = 40 IU

• 1 milligram = 40,000 IU

• nmol/L divided by 2.49 = ng/mL

• 100 IU D3 per day raises Calcidiol 1 ng/mL

• Vitamin D Deficiency: < 20 ng/mL 25(OH)D

• Vitamin D Insufficiency < 32 ng/mL

• 25(OH)D reference range 32-100

• 25(OH)D optimal range 60-100 ??

• What is one of the cheapest and easiest

interventions in medicine that would save

the most lives and the most money?

Inhibits Cutaneous Vitamin D

Production

• Clothing, Cultural Practices

• Sunscreen

• Latitude > 37 in winter, Early and late hours

• Skin pigmentation

• Body fat

• Age: 70 y/o produces 4 x less than 20 y/o

• Drugs

• Anticonvulsants, corticosteroids, rifampin

Few foods contain vitamin D

• Fish liver oils, such as

cod liver oil, 1 Tbs. (15 mL) provides 1,360 IU

• Fatty fish species, such as:

Herring, 85g (3 oz) provides 1383 IU

Catfish, 85g (3 oz) provides 425 IU

Salmon, cooked, 3.5 oz provides 360 IU

Mackerel, cooked, 3.5 oz, 345 IU

Sardines, canned in oil, drained, 1.75 oz, 250 IU

Tuna, canned in oil, 3 oz, 200 IU

Eel, cooked, 3.5 oz, 200 IU

• One whole egg, 20 IU

• Fortified Milk 100 IU/cup

• For every 100 IU ingested, 25(OH) D3 increases 1 ng/ml

Vitamin D Insufficiency

• At least 17 varieties of

cancer

• Heart disease, stroke,

hypertension

• Autoimmune diseases, MS

• Diabetes, type 1 and 2

• Depression

• Chronic pain

• Osteoarthritis

• Osteoporosis

• Muscle weakness

• Periodontal disease

• Childhood bone health

• Infectious disease

and more

Vitamin D Physiology

• Technically not a "vitamin"

• Vitamin D is in a class by itself.

• Its metabolic product, 1,25 dihydroxyvitamin

D = calcitriol, is a secosteroid hormone that targets

over 1000 genes

• Every cell has a vitamin D receptor that

responds to 1,25 dihydroxyvitamin D

Secosteroid hormone

Vitamin D3 = Cholecalciferol

“B” Ring is “Broken”

• Calcitriol Made in Kidneys via 25(OH) D3 -1-

hydroxylase

• Most potent steroid hormone in the human body

• First pathway:

• Calcitriol made by the kidney circulates in the blood to

maintain blood calcium levels

• Second Pathway:

• The second vitamin D pathway leads to cells and genomic

and non genomic effects and that is where all the action is.

• The amazing health benefits of vitamin D discovered

in the last 10 years are from vitamin D going down the

second pathway

The “Secret” Life of Vitamin D

Calcidiol

• Storage form of vitamin D

• Calcidiol is what fills your vitamin D gas tank.

• After your liver turns cholecalciferol into calcidiol

• Calcidiol follows one of two pathways.

• Calcidiol (25-hydroxyvitamin D) is a prehormone that

is directly made from cholecalciferol.

• When being tested for vitamin D deficiency, calcidiol is

the only blood test that should be drawn.

• When someone refers to vitamin D blood levels, they

are referring to calcidiol levels.

• Calcidiol is converted to calcitriol in many tissues, including prostate, colon, breast, lung, immune cells, monocytes, macrophages

• Regulates cell growth controls immune function, controls genome

• If Calcidiol is left over—if your tank is full and your kidneys are getting all the calcidiol they need to maintain serum calcium—then calcidiol is able to take the second pathway, one that leads directly to the cells.

• Avalanche of current research on calcitriol in cancer and autoimmune disease, infectious disease, diabetes, cardiovascular disease

• Autocrine and paracrine effects

Cholecalciferol = Vitamin D3

• Cholecalciferol is the naturally occurring form of

vitamin D.

• Cholecalciferol is made in large quantities in your skin when sunlight strikes bare skin.

• Can synthesize 20,000 IU per day by direct sun exposure at lower latitudes, especially with sweating in the sun

• It can also be taken as a supplement

• Ergocalciferol = Vitamin D2, which comes from ergosterol, the biological equivalent of cholesterol in fungal cell membranes when exposed to ultraviolet light.

• Not bioequivalent to D3, only reason to use D2 is to make Eli Lilly money.

Use Vitamin D3

• Supplementation should be with D3 not D2

– Trang, H., et al., “Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2. Amer Jour Clin Nutr 1998; 68:854-58.

– Armas, L., et al., “Vitamin D2 is much less effective than vitamin D3 in humans,” Jour Clin Endocrinol Metab 2004; 89:5387-391.

Safety of Vitamin D3 in adults

with multiple sclerosis.

• 28 weeks. Doses increased from 28,000 to:

• 280,000 IU/week = 40,000 IU/day

• Calcidiol rose from 31 to 155 ng/mL

• No hypercalcemia or other metabolic disturbance or toxicity

• Disease progression and activity were not affected, but the number of gadolinium-enhancing lesions per patient decreased from the initial mean of 1.75 to the end-of-study mean of 0.83 (P = 0.03).

Kimball, S. Safety of vitamin D3 in adults with multiple sclerosis Am J Clin Nutr. 2007 Sep;86(3):645-51

Molecular Actions of Vitamin D

• Contributing to Cancer Prevention

• Vitamin D or metabolites have direct inhibitory action on initiation and progression of various cancers

• Renal production of Calcitriol regulates Calcium metabolism with PTH

• Extra renal production of Calcitriol relates to cancer risk

• Calcitriol is anti-inflammatory and turns off NFKB

• Growth Arrest of malignant cells

Fleet, James PhD. Molecular Actions of Vitamin D Contributing to Cancer Prevention. Molecular Aspects of Medicine. 2008

• Cell Junction effects

• Apoptosis

• Anti-Metastasis

• Primary molecular action of Calcitriol is binding to Vitamin D Receptor (VDR) , a member of steroid hormone receptor superfamily

• Initiates gene transcription

• VDR needed for growth arrest of cancer

• Calcitriol also has non-genomic rapid actions

• Binds to cell membrane

• VDR turns on genes for increase in production of IGFBP-3

• Cancer can turn off CYP27b1 inhibiting Calcitriol production

Cancer

• Grant proposes in this article that 23,000 American lives

per year could be saved from a reduction in cancer

mortality by supplementing with vitamin D or

providing adequate exposure to UV light.

– Grant, W., “The association of solar ultraviolet B (UVB) with reducing risk of

cancer: multifactorial ecologic analysis of geographic variation in age-adjusted

cancer mortality rates,” Anticancer Res 2006; 26:2687-699.

• Garland, et., al in their article discuss that if everyone had a 25 OH vitamin D level that is > or equal to 55 ng/mL there would be at least 60,000 cases per year of colorectal cancer and 85,000 cases per year of breast cancer that would be prevented in North America.

• This same article goes on to say that the projected number of cases that could be prevented annually in the world with this serum level of vitamin D would be approximately 250,000 cases of colorectal cancer and 350,000 cases of breast cancer.

—Garland, C., et al., “What is the dose-response relationship between vitamin D and cancer risk? Nutrition Reviews 2007; 65(8):S91-S95.

Cancer